Role of Pseudomonas aeruginosa Glutathione Biosynthesis in Lung and Soft Tissue Infection

Abstract

The opportunistic pathogen <i>Pseudomonas aeruginosa</i> is a leading cause of morbidity and mortality worldwide. To survive in both the environment and the host, <i>P. aeruginosa</i> must cope with redox stress. In <i>P. aeruginosa</i>, a primary mechanism for protection from redox stress is the antioxidant glutathione (GSH). GSH is a low-molecular-weight thiol-containing tripeptide (l-γ-glutamyl-l-cysteinyl-glycine) that can function as a reversible reducing agent. GSH plays an important role in <i>P. aeruginosa</i> physiology and is known to modulate several cellular and social processes that are likely important during infection. However, the role of GSH biosynthesis during mammalian infection is not well understood. In this study, we created a <i>P. aeruginosa</i> mutant defective in GSH biosynthesis to examine how loss of GSH biosynthesis affects <i>P. aeruginosa</i> virulence. We found that GSH is critical for normal growth <i>in vitro</i> and provides protection against hydrogen peroxide, bleach, and ciprofloxacin. We also studied the role of <i>P. aeruginosa</i> GSH biosynthesis in four mouse infection models, including the surgical wound, abscess, burn wound, and acute pneumonia models. We discovered that the GSH biosynthesis mutant was slightly less virulent in the acute pneumonia infection model but was equally virulent in the three other models. This work provides new and complementary data regarding the role of GSH in <i>P. aeruginosa</i> during mammalian infection.